Challenges During Review of COVID-19 Research Proposals: Experience of Faculty of Medicine, Ain Shams University Research Ethics Committee, Egypt.

The COVID-19 pandemic resulted in an overwhelming increase in research studies submitted to research ethics committees (RECs) presenting many ethical challenges. This article aims to report the challenges encountered during review of COVID-19 research and the experience of the Faculty of Medicine, Ain Shams University Research Ethics Committee (FMASU REC). From April 10, 2020, until October 13, 2020, the FMASU REC reviewed 98 COVID-19 research protocols. This article addressed the question of how to face an overwhelming amount of research submitted to the REC while applying the required ethical principles. Ethical challenges included a new accelerated mode of review, online meetings, balance of risks vs. benefits, measures to mitigate risks, co-enrolment in different studies, protection of a vulnerable COVID-19 population, accelerated decisions, online research, how to handle informed consent during the pandemic, and justification of placebo arm.

A cross-sectional household cluster serosurvey of hepatitis C virus antibodies in an urban slum of Cairo, Egypt in 2004.

BACKGROUND: Hepatitis C Virus (HCV) continues to be a burden to the Egyptian population and its economy. Despite all efforts, the prevalence of infection continues to be one of the highest in the world. The high national prevalence has been attributed to unintentional, nosocomial spread during an anti-schistosomiasis campaign conducted in the 1970's, but that does not fully explain the persistent infection rates. Work is needed to further clarify risk associations. A serosurvey was performed in Manshiet Nasser, a slum in Cairo sometimes referred to as Mokattem Hills where a primary occupation is garbage collection and sorting, to characterize potential risk factors for infection. METHODS: Following a detailed mapping and census of the area, a cluster sampling was performed and demographic and risk behavior data and a blood sample were collected from subjects older than 6 months. Blood samples were tested using 4th generation anti-HCV EIA kit. RESULTS: The slum was estimated to house 45,000 residents. Blood samples were obtained from 2169 subjects. The age adjusted anti-HCV seroprevalence was 9.1 %. Participants with HCV antibodies were more likely to be male, heads of households, subjects without formal education, and those with a lower standard of living. After adjustment of all prevalence ratios (aPR) for age, the following risk factors were significantly associated with higher risk of HCV infection: Garbage collection (aPR 1.5), history of blood transfusion (aPR 2.0), tattooing (aPR 1.4), history of schistosomiasis (aPR 1.5), and use of traditional latrines (aPR 2.0) or pits for sanitation (aPR 1.3). The results of the multivariate analysis indicated that age (p < 0.01), history of schistosomiasis (p < 0.05), garbage sorting (p = 0.05), blood transfusions (<0.001), and the use of traditional latrines for sanitation (p < 0.01) were significantly associated with infection. CONCLUSION: While HCV prevalence among those over 30 could be attributed to anti-schistosomiasis injections, the prevalence in younger age indicates ongoing transmission. Although specific behavioral risks were not identified, HCV infection appears to be an occupational hazard of garbage collection and sorting in this environment. Given the large reservoir of HCV infection in the population, further effort needs to be made to identify and mitigate new infections.

Phenotypic and genotypic characterization of enterotoxigenic Escherichia coli isolated from U.S. military personnel participating in Operation Bright Star, Egypt, from 2005 to 2009.

Enterotoxigenic Escherichia coli (ETEC) is a major health problem for travelers to the Middle East. During the autumn months of 2005, 2007, and 2009, U.S. military personnel participated in Operation Bright Star (OBS) exercises in Egypt. Out of 181 military personnel enrolled in a diarrheal surveillance study, E. coli-like colonies were isolated from 170 patients. Isolates were tested for the detection of ETEC enterotoxins and colonization factors (CFs) using phenotypic and genotypic methods. Additionally, we studied the secular trends of ETEC isolates obtained from OBS studies since 1999. ETEC was isolated from 51.2% and 60.0% of the patients based on enzyme-linked immunosorbent assay and polymerase chain reaction (PCR), respectively. Heat stable (ST) was the dominant enterotoxin detected followed by heat labile (LT) and LTST. Additionally, we detected a CF in 59.7% and 67.6% of the ETEC-positive isolates using dot blot and PCR assays, respectively. The predominant CF isolated was CS6 followed by CS3.

Hotel clinic-based diarrheal and respiratory disease surveillance in U.S. service members participating in Operation Bright Star in Egypt, 2009.

We conducted clinic-based, influenza-like illness and diarrheal disease surveillance among U.S. service members participating in Operation Bright Star 2009. Epidemiologic data and samples were collected. Nasopharyngeal swab specimens were tested for viruses, and feces was tested for microbiologic, immunologic, and molecular diagnostics. A survey was used to collect self-reported data. From 1,529 surveys, 41% reported diarrheal disease and 25% reported respiratory illness (incidence rate = 62 of 100 versus 37 of 100 person-months; incidence rate ratio = 1.7, 95% confidence interval = 1.5-1.9). Enterotoxigenic Escherichia coli was identified in 74% (69 of 93) of fecal samples. In the influenza-like illness case series, 17% (9 of 52) were positive for influenza A; all were positive for pandemic (pH1N1) 2009 virus. Rates of decreased work performance reported by patients with diarrhea and influenza-like illness were similar (46% versus 48%; P = 0.8). Diarrheal diseases and respiratory illness remain common among deployed military personnel, with important operational impact. Despite an ongoing influenza pandemic, diarrheal disease incidence was higher than that of respiratory illness.

Specific IgA antibodies in the diagnosis of acute brucellosis.

An Egyptian female with night sweats, headache, and back pain was diagnosed with acute brucellosis one week after returning from a North African country. Humoral immune responses to specific immunogenic proteins were investigated before and after treatment. ELISA was performed to detect levels of specific antibody (Ab) titers. Immunoblot analysis of Ab recognizing specific Brucella antigenic bands was also performed. IgA was detected on the day of disease onset. Specific agglutination titer was 1:160; it doubled three days later and treatment was implemented. Blood culture yielded Gram-negative coccobacilli after one month, confirmed as B. melitensis by AMOS-PCR. Immunoblotting revealed IgM Abs against two protein bands of 112 and 130-kDa observed only during the acute stage. On the other hand, the intensity of IgG Abs against 21 and 21.5-kDa protein bands positively correlated with the time of convalescence. Based on our observations we conclude that specific IgA levels may be used as an early diagnostic marker for Brucella and high molecular weight protein bands may be useful in the differentiation between acute and chronic brucellosis.

Validation of the Dri-Dot Latex agglutination and IgM lateral flow assays for the diagnosis of typhoid fever in an Egyptian population.

Laboratory confirmation of typhoid fever is essential for appropriate medical treatment. Blood culture is a standard test for diagnosis of typhoid fever, but well-equipped diagnostic facilities to perform culture are seldom available in endemic areas. We retrospectively compared 2 diagnostic field tests, a latex agglutination Dri-Dot assay and an IgM Lateral Flow assay, to blood culture, in patients with clinically diagnosed typhoid fever. Sensitivity of the Dri-Dot was 71.4%, and specificity was 86.3% for samples collected at time of first diagnosis. Sensitivity and specificity of IgM Lateral Flow were 80% and 71.4%, respectively. A major limitation of these serologic tests is the limited sensitivity at the early stage of the disease. Performing both tests in parallel increased sensitivity to 84.3%, but decreased specificity to 70.5%. There was a trend towards improved diagnostic performance using either assay over a longer duration of illness. These rapid, point-of-care assays for typhoid fever provide easy-to-interpret results in typhoid-endemic countries and may be most useful in patients presenting 1 week after symptom onset.

Antimicrobial resistance surveillance in the AFHSC-GEIS network.

International infectious disease surveillance has been conducted by the United States (U.S.) Department of Defense (DoD) for many years and has been consolidated within the Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) since 1998. This includes activities that monitor the presence of antimicrobial resistance among pathogens. AFHSC-GEIS partners work within DoD military treatment facilities and collaborate with host-nation civilian and military clinics, hospitals and university systems. The goals of these activities are to foster military force health protection and medical diplomacy. Surveillance activities include both community-acquired and health care-associated infections and have promoted the development of surveillance networks, centers of excellence and referral laboratories. Information technology applications have been utilized increasingly to aid in DoD-wide global surveillance for diseases significant to force health protection and global public health. This section documents the accomplishments and activities of the network through AFHSC-GEIS partners in 2009.

Enteric disease surveillance under the AFHSC-GEIS: current efforts, landscape analysis and vision forward.

The mission of the Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) is to support global public health and to counter infectious disease threats to the United States Armed Forces, including newly identified agents or those increasing in incidence. Enteric diseases are a growing threat to U.S. forces, which must be ready to deploy to austere environments where the risk of exposure to enteropathogens may be significant and where routine prevention efforts may be impractical. In this report, the authors review the recent activities of AFHSC-GEIS partner laboratories in regards to enteric disease surveillance, prevention and response. Each partner identified recent accomplishments, including support for regional networks. AFHSC/GEIS partners also completed a Strengths, Weaknesses, Opportunities and Threats (SWOT) survey as part of a landscape analysis of global enteric surveillance efforts. The current strengths of this network include excellent laboratory infrastructure, equipment and personnel that provide the opportunity for high-quality epidemiological studies and test platforms for point-of-care diagnostics. Weaknesses include inconsistent guidance and a splintered reporting system that hampers the comparison of data across regions or longitudinally. The newly chartered Enterics Surveillance Steering Committee (ESSC) is intended to provide clear mission guidance, a structured project review process, and central data management and analysis in support of rationally directed enteric disease surveillance efforts.

A randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of rifaximin for the prevention of travelers' diarrhea in US military personnel deployed to Incirlik Air Base, Incirlik, Turkey.

BACKGROUND: Infectious diarrhea is an important problem among travelers and deployed US military overseas causing substantial morbidity due to acute illness and may result in burdensome postinfectious sequelae. METHODS: The nonsystemic antibiotic rifaximin was evaluated for prevention of travelers' diarrhea (TD) in a US military and civilian adult beneficiary population in a randomized, double-blind, placebo-controlled clinical trial. In all, 100 volunteers deployed to Incirlik Air Base, Turkey, received rifaximin 1,100 mg once daily or placebo for 2 weeks, and participants were followed daily for 2 weeks. RESULTS: In an intention to treat analysis (n = 95), TD (based on subjects meeting case definition or early treatment) developed in 6.3% (3 of 48) of the rifaximin group compared with 19.2% (9 of 47) in the placebo group (Fisher's exact test p = 0.07). Rifaximin provided 67% (95% confidence interval, -13% to 91%, p = 0.07) protection against TD. Rifaximin 1,100 mg once daily was well tolerated with no observed differences in adverse events, whether solicited or unsolicited among the two treatment groups. CONCLUSIONS: Rifaximin may represent an option among military personnel on deployment for prevention of TD with supportive future studies that consider deployment length, settings, and operational situations where widespread use of chemoprophylaxis may increase force health protection without undue risk during critical deployments.

The changing epidemiology of meningococcal meningitis after introduction of bivalent A/C polysaccharide vaccine into school-based vaccination programs in Egypt.

BACKGROUND: The strategy recommended by the World Health Organization (WHO) to curtail outbreaks of meningococcus in Africa is enhanced surveillance with administration of oily chloramphenicol as well as vaccination when incidence thresholds are exceeded. The role of capsular polysaccharide meningococcal vaccine in outbreak prevention has been the subject of considerable debate. The Egyptian Ministry of Health and Population initiated a school-based vaccination program with bivalent A/C capsular polysaccharide vaccine in 1992. This investigation reviews data on meningococcal meningitis in Egypt comparing years before and after introduction of the vaccine. METHODS: This is a retrospective review of several sources to examine the rates and serogroups of meningococcal meningitis before and after the introduction of the meningococcal A/C vaccine in Egypt. FINDINGS: Between 1967 and 1991, outbreaks of meningococcal disease were documented with a periodicity of 8 years in Egypt. However, there has not been an outbreak since 1991 and over the same period, there has also been a progressive decline in the baseline incidence of meningococcus. Also, a shift from a serogroup A to serogroup B predominance in meningococcal disease was noted during the study period. These data suggest that there has been an alteration in the epidemiology of meningococcal disease in Egypt that coincided with the implementation of the school-based vaccination program. INTERPRETATION: Routine use of the bivalent A/C meningococcal vaccine may be an alternative for the control and prevention of meningococcal disease in high-risk areas including the "meningitis belt".

Relationship between intracranial granulomas and cerebrospinal fluid levels of gamma interferon and interleukin-10 in patients with tuberculous meningitis.

Cerebrospinal fluid gamma interferon (IFN-gamma) and interleukin-10 levels in 39 patients with tuberculous meningitis were serially measured. Cytokine levels did not predict intracranial granuloma (IG) development, but IFN-gamma levels in the top quartile after 1 month of therapy were highly associated (odds ratio = 18) with detection of an IG by computed tomography scanning.

Short-course azithromycin for the treatment of uncomplicated typhoid fever in children and adolescents.

We studied 149 children and adolescents 3-17 years of age with clinical typhoid fever who were treated with either oral azithromycin (20 mg/kg per day; maximum dose, 1000 mg/day) or intravenous ceftriaxone (75 mg/day; maximum dose, 2.5 g/day) daily for 5 days. Blood and stool specimens were obtained for culture before the initiation of therapy and were repeated on days 4 and 8 of treatment. Isolation of Salmonella enterica serovar Typhi or S. enterica serovar Paratyphi from the initial culture was required for inclusion in the final analysis. S. Typhi was isolated from 68 patients, 32 of whom were receiving azithromycin. Cure was achieved in 30 (94%) of 32 patients in the azithromycin group and in 35 (97%) of 36 patients in the ceftriaxone group (P=NS). Mean time to clearance of bacteremia was longer in the azithromycin group than in the ceftriaxone group. No patient who received azithromycin had a relapse, compared with 6 patients who received ceftriaxone. A 5-day course of azithromycin was found to be an effective treatment for uncomplicated typhoid fever in children and adolescents.

Rapid diagnosis of typhoid fever by enzyme-linked immunosorbent assay detection of Salmonella serotype typhi antigens in urine.

We developed and evaluated an enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies to capture somatic antigen 9 (O9), flagellar antigen d (Hd), and the Vi capsular polysaccharide antigen (Vi) from the urine of persons with and without typhoid fever. Sequential urine samples were collected from 44 patients with blood culture-confirmed typhoid fever and from two control groups. The first control group included patients with brucellosis (n = 12) and those with clinically diagnosed, non-typhoid, acute, febrile illness (n = 27). The second control group was a sample of healthy volunteer laboratory workers (n = 11). When assessed relative to date of fever onset, sensitivity was highest during the first week for all three antigens: Vi was detected in the urine of nine (100%) patients, O9 in 4 (44%) patients, and Hd in 4 (44%) patients. Sequential testing of two urine samples from the same patient improved test sensitivity. Combined testing for Vi with O9 and Hd produced a trend towards increased sensitivity without compromising specificity. The specificity for Vi exceeded 90% when assessed among both febrile and healthy control subjects, but was only 25% when assessed among patients with brucellosis. Detection of urinary Vi antigen with this ELISA shows promise for the diagnosis of typhoid fever, particularly when used within the first week after fever onset. However, positive reactions for Vi antigen in patients with brucellosis must be understood before urinary Vi antigen detection can be developed further as a useful rapid diagnostic test.

Fluconazole for the treatment of Cryptococcus neoformans meningitis in an immunocompetent host.

We present a case of a 23-year-old immunocompetent male who presented with chronic meningitis and was diagnosed as cryptococcal meningitis by positive cryptococcal antigen titer. The cerebrospinal fluid culture was positive for Cryptococcus neoformans. He was treated initially with amphotericin B but was later changed to fluconazole due to toxicity. This case highlights the use of fluconazole to successfully treat chronic meningitis in an immunocompetent host.